At least one hundred hypertensive patients with renal disease (creatinine 1.6-7 micrograms/dl) will enter the protocol "Plasma Norepinephrine as a Renal Risk Factor". They will be randomly distributed into two groups with equal stratification of risk factors for progression of renal disease. One half of the patients will have plasma norepinephrine suppressed by clonidine and the other one-half will be treated with agents that have either no effect on plasma norepinephrine or will raise plasma norepinephrine. The goal is to determine if inhibition of norepinephrine release decreases the rate of progression of renal disease in these patients. In the second project we will complete the titration of prazosin and initiate the titration with captopril in minoxidil-treated patients. The immediate goal of this project is to learn to predictably lower blood pressure of severely hypertensive patients to predetermined levels. On the basis of this information, by July 1981 we expect to have completed development of a protocol which will permit a predictable reduction of diastolic blood pressure, without disabling side effects, to the range of 65-78 for one group and to 79-90 with another group of intermediate-severely hypertensve patients with renal disease. The ultimate goal of this project is answer the question "to what extent should blood pressure be lowered" particularly in patients with tragic risk of renal failure.